The present invention relates to hydrophilic substances containing perfluoro compounds and to methods of making emulsions containing perfluoro compounds.
In U.S. Pat. No. 4,855,326, issued Aug. 8, 1989 various substances having pharmacological properties were combined with a sugar and spun into fibers to produce a readily water-soluble product. The various examples enumerated in the patent all involved the use of water soluble medicaments and were directed to enhancing the solubility rate of the different substances. The patent describes methods for combining a medicament with any one or more of the water soluble melt spinnable sugars and spinning the combination to produce a readily soluble floss form of the medicament. The disclosure of such patent is incorporated herein by reference.
In co-pending application Ser. No. 07/283,742, filed Dec. 13, 1988, now U.S. Pat. No. 5,011,532, issued Apr. 30, 1991, the disclosure deals with oleaginous substances such as vegetable oil, baby oil, olive oil, margarine, lanolin, cocoa butter, and the like, and how their lack of affinity for water is altered by mixing the oleaginous substance with sugar and melt spinning the mixture in a cotton candy spinning machine or the equivalent. As so modified the products disperse autogenously in water forming a colloidal or pseudo-colloidal dispersion. Such modification enabled such widely disparate procedures as: (a) incorporating shortening oil in a cake mix containing flour but no egg to which water is added to produce a batter; and (b) producing a confection or medicated lozenge by dehydrating the dispersion and allowing the melted residue to solidify. The aforementioned application discloses that any oleaginous substance that can be mixed with a melt-spinnable sugar, when spun in a cotton candy spinning machine, produces a product which, when added to water or has water added to it, forms, virtually autogenously, a uniform dispersion having all the appearances of a colloidal dispersion. The disclosure of such application is incorporated herein by reference.
Other disclosures dealing with spinning substances with one or more sugars will be found in U.S. Pat. No. 4,873,085, issued Oct. 10, 1989, and in co-pending applications, Ser. Nos.: 07/325,643; 07/392,427; and 07/444,045; filed, respectively, Mar. 20, 1989; Aug. 10, 1989; and Nov. 30, 1989, now, respectively, U.S. Pat. Nos. 5,034,421; 5,028,632; and 4,997,856.
In application Ser. No. 07/325,643 it is explained that a spun product from a combination of a saccharide and a hydrophobic ingredient is hydrophilic with low concentrations of such ingredient but becomes increasingly hydrophobic as the concentration of the hydrophobic ingredient is increased, although the end product nevertheless acts hydrophilically when the water temperature is elevated. Beeswax is disclosed in the -643 application as being a moderating agent. As described therein, pure white pharmaceutical grade beeswax, a substance that is essentially hydrophobic, was mixed with sucrose and spun, producing an excellent floss which floated when added to normal room temperature water, but immediately dispersed with the appearance of being colloidal when added to water at about 180.degree. F. (82.2.degree. C.).
In the Kirk-Othmer Encyclopedia of Chemical Technology, 3rd ed., Suppl. Vol.-Alcohol Fuels to Toxicology, published by John Wiley & Sons, Copr. 1984, there appears, on pp. 159-171, an article entitled "Blood-Replacement Preparations" by Robert Geyer of Harvard University. The article deals with liquid perfluoro compounds which have been investigated for biomedical application. These nonpolar materials dissolve appreciable quantities of gases such as oxygen and carbon dioxide. The article lists 18 different compounds in a table on page 162 which compounds are identified as suitable for blood-replacement preparations. Among the compounds mentioned are: the perfluoro derivatives of dimethyladamantane, formula C.sub.12 F.sub.20 ; tributylamine, formula C.sub.12 F.sub.27 N; dihexyl ether, formula C.sub.12 F.sub.26 O; and l-bromooctane, formula C.sub.8 F.sub.17 Br. All of the mentioned perfluoro compounds are colorless and odorless liquid organic compounds in which all hydrogens have been replaced with fluorine. They are essentially insoluble in water and other polar liquids. To provide a perfusion liquid the perfluoro compound has to be emulsified and this has required an emulsifying agent. The emulsifying agents must be strictly nontoxic for biomedical use. Frequently used emulsifying agenta are phospholipids such as egg-yolk phospholipids.
A proprietary product, "Pluronic F-68" produced by BASF Wyandotte Corp., is mentioned in the above article, and stated to be the most frequently used surfactant for blood-replacement preparations. However, the article states that the purified form of the surfactant must be stored at -25.degree. C. or lower, preferably under nitrogen. The restriction on utility should be self-evident.
Use of the egg-yolk phospholipids has encountered problems in that experiments have uncovered a high rate of adverse human reaction to the phospholipids. Thus, prior to the present invention it has not been possible to produce a satisfactory in vivo perfusion liquid suitable for transfusion which is based on a perfluoro compound.